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Abstract Background Low body mass index has been associated with increased mortality in severe COPD. The impact of body composition earlier in the disease remains unclear. We studied the impact of body composition on the risk of functional limitation in COPD. Methods We used bioelectrical impedance to estimate body composition in a cohort of 355 younger adults with COPD who had a broad spectrum of severity. Results Among women, a higher lean-to-fat ratio was associated with a lower risk of self-reported functional limitation after controlling for age, height, pulmonary function impairment, race, education, and smoking history (OR 0.45 per 0.50 increment in lean-to-fat ratio; 95% CI 0.28 to 0.74). Among men, a higher lean-to-fat ratio was associated with a greater distance walked in 6 minutes (mean difference 40 meters per 0.50 ratio increment; 95% CI 9 to 71 meters). In women, the lean-to-fat ratio was associated with an even greater distance walked (mean difference 162 meters per 0.50 increment; 95% CI 97 to 228 meters). In women, higher lean-to-fat ratio was also associated with better Short Physical Performance Battery Scores. In further analysis, the accumulation of greater fat mass, and not the loss of lean mass, was most strongly associated with functional limitation among both sexes. Conclusion Body composition is an important non-pulmonary impairment that modulates the risk of functional limitation in COPD, even after taking pulmonary function into account. Body composition abnormalities may represent an important area for screening and preventive intervention in COPD.

Purpose: Radiographic features in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) are well described, but less is known in bisphosphonate-exposed individuals with stage 0 disease (clinical symptoms without exposed necrotic bone) considered at risk for BRONJ. We sought to characterize radiographic findings in a subgroup of patients with concerning clinical symptoms and bisphosphonate exposure to identify imaging features that may presage development of BRONJ. Materials and Methods: A dental symptom survey was returned by 8,572 Kaiser Permanente Health Plan members receiving chronic oral bisphosphonate therapy, and 1,005 patients reporting pertinent dental symptoms or complications after dental procedures were examined. Those without BRONJ but with concerning symptoms were referred for clinical evaluation, including imaging. Among the subset who received maxillofacial imaging, we identified those with stage 0 disease and abnormal radiographic features. Results: There were a total of 30 patients without exposed bone but with concerning symptoms who received maxillofacial imaging (panoramic radiography or computed tomography) in the context of clinical care. Among these 30 patients, 10 had stage 0 disease with similar radiographic features of regional or diffuse osteosclerosis in clinically symptomatic areas, most with extension beyond the involved site. Other findings in these 10 patients included density confluence of cortical and cancellous bone, prominence of the inferior alveolar nerve canal, markedly thickened and sclerotic lamina dura, uniform periradicular radiolucencies, cortical disruption, lack of bone fill after extraction, and a persisting alveolar socket. None had exposed bone develop during 1-year follow-up. The remaining 20 patients had normal or localized radiographic findings consistent with odontogenic pathology. Conclusion: In 10 of 30 symptomatic patients referred for clinical evaluation and imaging, a consistent finding was conspicuous osteosclerosis in clinically symptomatic areas characteristic of stage 0 disease. These data support the need to better understand radiographic features associated with bisphosphonate exposure and to determine whether osteosclerosis is a specific finding indicative of the risk for progression to BRONJ. [Copyright &y& Elsevier]

Purpose: Osteonecrosis of the jaw (ONJ) is a serious complication associated with bisphosphonate therapy, but its epidemiology in the setting of oral bisphosphonate therapy is poorly understood. The present study examined the prevalence of ONJ in patients receiving chronic oral bisphosphonate therapy. Materials and Methods: We mailed a survey to 13,946 members who had received chronic oral bisphosphonate therapy as of 2006 within a large integrated health care delivery system in Northern California. Respondents who reported ONJ, exposed bone or gingival sores, moderate periodontal disease, persistent symptoms, or complications after dental procedures were invited for examination or to have their dental records reviewed. ONJ was defined as exposed bone (of >8 weeks'' duration) in the maxillofacial region in the absence of previous radiotherapy. Results: Of the 8,572 survey respondents (71 ± 9 years, 93% women), 2,159 (25%) reported pertinent dental symptoms. Of these 2,159 patients, 1,005 were examined and an additional 536 provided dental records. Nine ONJ cases were identified, representing a prevalence of 0.10% (95% confidence interval 0.05% to 0.20%) among the survey respondents. Of the 9 cases, 5 had occurred spontaneously (3 in palatal tori) and 4 occurred in previous extraction sites. An additional 3 patients had mandibular osteomyelitis (2 after extraction and 1 with implant failure) but without exposed bone. Finally, 7 other patients had bone exposure that did not fulfill the criteria for ONJ. Conclusions: ONJ occurred in 1 of 952 survey respondents with oral bisphosphonate exposure (minimum prevalence of 1 in 1,537 of the entire mailed cohort). A similar number had select features concerning for ONJ that did not meet the criteria. The results of the present study provide important data on the spectrum of jaw complications among patients with oral bisphosphonate exposure. [Copyright &y& Elsevier]

Purpose: Although chronic obstructive pulmonary disease (COPD) has a major impact on physical health, the specific impact of COPD on physical functional limitations has not been characterized clearly. We aimed to elucidate the physical functional limitations that are directly attributable to COPD compared to a matched referent group without the condition., Methods: We used the Function, Living, Outcomes, and Work (FLOW) cohort study of adults with COPD (n=1202) and referent subjects matched by age, sex, and race (n=302) to study the impact of COPD on the risk of a broad array of functional limitations using validated measures: lower extremity function (Short Physical Performance Battery [SPPB]), submaximal exercise performance (Six Minute Walk Test [SMWT]), standing balance (Functional Reach Test), skeletal muscle strength (manual muscle testing with dynamometry), and self-reported functional limitation (standardized item battery). Multivariate analysis was used to control for confounding by age, sex, race, height, educational attainment, and cigarette smoking., Results: COPD was associated with poorer lower extremity function (mean SPPB score decrement for COPD vs referent -1.0 points; 95% CI, -1.25 to -0.73 pts) and less distance walked during the SMWT (-334 feet; 95% CI, -384 to -282 ft). COPD also was associated with weaker muscle strength in every muscle group tested, including both the upper and lower extremities (P<.0001 in all cases) and with a greater risk of self-reported functional limitation (OR 6.4; 95% CI, 3.7 to 10.9)., Conclusions: A broad array of physical functional limitations were specifically attributable to COPD. COPD affects a multitude of body systems remote from the lung.

Atrial natriuretic peptide (ANP) has been implicated in the development of hypertension in Dahl R and S rats. To test the responses of DR and DS kidneys in the absence of the influence of neural and humoral mechanisms, we investigated the pharmacokinetics and pharmacodynamics of ANP in isolated perfused DR and DS kidneys, obtained from rats given a high or low sodium diet, after a bolus injection of ANP (1 microgram) or after a bolus injection plus infusion of ANP to maintain the perfusate concentration at 1000 pg/ml. The elimination rate constant was not different between the groups (DR, 0.044 min-1 vs. DS, 0.050 min-1). Clearance of ANP was 4 times greater than the glomerular filtration rate, indicating that a receptor-mediated peritubular clearance is probably the primary route of elimination. DS kidneys excreted 50% less sodium than DR kidneys. However, ANP caused a 5-fold increase in fractional sodium excretion in both DR and DS. ANP also increased sodium excretion, creatinine clearance, and urine flow. No alteration in ANP kinetics occurred to account for the reportedly increased circulating concentrations of ANP seen in DS rats. We conclude that isolated DR and DS kidneys respond differently to ANP after bolus ANP administration to concentrations of 10,000 pg/ml. This difference in response is due to the sodium excretory defect inherent in the DS kidney and not to an alteration in the DS kidney's ANP responsiveness.

Physical activity is important for maintenance of bone mass. The effects of exercise on bone histomorphometry were studied in 9-month-old intact (INT) and ovariectomized (OVX) rats. The rats were either kept sedentary (SED) or were exercised (EX) on a treadmill at 21 m/min for 1 h/day 5 days/week for 3 months. Bone resorption as well as formation parameters were significantly higher in OVX-SED than in INT-SED rats, indicating increased bone turnover in OVX rats. In OVX rats, lower osteoclast perimeter and number, lower labeled perimeter but higher mineral apposition rate (MAR) and bone formation rate (BFR) were associated with higher trabecular bone in OVX-EX compared with OVX-SED rats. In intact rats, trabecular bone mass and osteoclast number and perimeter were not affected by exercise. Labeled perimeter was slightly lower while MAR was higher and BFR was insignificantly higher in INT-EX than in INT-SED rats. Thus, exercise resulted in fewer resorption-formation sites, as indicated by lower labeled perimeter, but higher activity of individual osteoblasts, as indicated by higher MAR, both in estrogen-depleted and estrogen-replete states.